The purpose of this proposed research is to elucidate in chemical terms some of the changes which accompany diffuse intravascular coagulation that underlies thromboembolic phenomena. A single protein, factor V, has been selected since it is necessary for thrombin formation and is in turn activated by thrombin. This positive feedback may constitute an important regulatory mechanism. The chemistry and interconvertibility of the different molecular forms of purified bovine V will be further explored to increase our understanding of the relationship of one form to the other and their physiologic role. Factor V must combine with phospholipid and calcium in order to accelerate conversion of prothrombin to thrombin. Therefore, the binding of each form of factor V with phospholipid will be studied by gel filtration and activity measurement. The phospholipids associated with the forms of factor V will be characterized by thin layer and gas liquid chromatography. The role of each form of factor V will be delineated in the intrinsic system as well as the extrinsic system. The molecular changes during the increase of activity of factor V catalyzed by thrombin will be examined. Changes including size, change, end groups, conformational state, and release of peptides will be sought.